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Tools and Methods for the Elucidation of Fatty Acid Amide Cell Signaling Pathways

阐明脂肪酸酰胺细胞信号通路的工具和方法

基本信息

批准号：
10310497
负责人：
James Leahy
金额：
$ 17.66万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-05 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10310497
关键词：
Active Sites Afferent Neurons Alkynes Amides Amines Amino Acids Anabolism Antibodies Area Binding Binding Proteins Biogenic Amines Biological Models Biomedical Research CNR1 gene Calcium Carrier Proteins Cells Coupled Data Development Drosophila melanogaster Drug Targeting Ensure Enzymes Family Fatty Acids Funding Future Goals Health Human Individual Invertebrates Investigation Label Ligand Binding Ligands Lipids Locomotion Mechanics Membrane Metabolism Methods Modification Mus N-palmitoylglycine Neuroblastoma Nitric Oxide Nucleotides Orphan Parents Pharmaceutical Preparations Play Positioning Attribute Process Production Proteins Proteome Proteomics Research Role Signal Pathway Signal Transduction Sleep Specificity Structure System Tissues United States National Institutes of Health Validation Vertebrates Visualization Work analog anandamide base bropirimine design drug discovery experience fatty acid-transport protein flexibility improved in vivo innovative technologies insight long chain fatty acid member new therapeutic target novel oleylamide receptor receptor binding tool

项目摘要

Abstract: Cell signaling is one of the most fundamental processes that controls human health, and yet the mechanics of this intricate system is largely unappreciated. This is stunning because the primary agents for this system, membrane receptors, are known to account for approximately 1/3 of all approved human drugs. Often, the receptors themselves are known before the discovery of their endogenous ligands. In this proposal, we detail a systematic method for the identification of the targets of fatty acid amides, a highly regulated class of molecules known to engage in at least two signaling processes. The bulk of the other members of this class of compounds have never been paired with their receptors, and uncovering this information has tremendous potential for identifying new therapeutic targets and improving drug discovery efforts by revealing potentially undesirable off-target candidates.

摘要：细胞信号传导是控制人类健康的最基本的过程之一，然而，这个复杂的系统在很大程度上没有得到重视。这是惊人的，因为这个系统的主要代理人，已知膜受体占所有批准的人用药物的约1/3。往往受体本身在发现其内源性配体之前是已知的。在这个建议中，我们详细介绍了一个系统的方法，用于识别脂肪酸酰胺的目标，一个高度已知参与至少两个信号传导过程的受调节的分子类别。另一个的大部分这类化合物的成员从未与它们的受体配对，信息在识别新的治疗靶点和改进药物发现方面具有巨大的潜力通过揭示潜在的不受欢迎的脱靶候选人的努力。